Neuronal and retinal tissue are high in phospholipids containingone or two long chain polyunsaturated acyl chains. A further refinement of our analysis of the time-resolved anisotropy decay of the hydrophobic fluorescence probe diphenylhexatriene (DPH) allows a measure of the acyl chain packing order in the membrane interior vs the portion of the chain closer to the interfacial region. Polyunsaturated acyl chains result in the highest degree of acyl chain disorder and produce the highest values of acyl chain packing free volume, a parameter which promotes the greatest degree of formation of the activate conformation of the G protein-coupled receptor, rhodopsin. Cholesterol has been shown to decrease both acyl chain packing free volume and rhodopsin activation. Our studies show that polyunsaturated phospholipids are able to resist the ordering effects of cholesterol and maintain their unique acyl chain packing properties. Recent findings demonstrate that acyl chain packing is increased by increased osmotic stress, due to the dehydration of the phospholipid head group. Ethanol on the other hand has an antagonistic effect of decreasing acyl chain order. These effects are important in understanding in vivo mechanisms of alcohol action since ethanol effects occur in the presence of an osmotic background of plasma. These findings have important implications for integral membrane protein function and suggest that highly unsaturated phospholipids found in retina and neuronal tissue can optimize receptor function, are able to resist the effects of certain compositional variation, such as increases in cholesterol content, and may modulate membrane sensitivity to ethanol. - neurosciences, nutritional disorders